ION CHANNELS IN THE NERVOUS SYSTEM

描述：神经系统中几乎所有的离子通道都是 多基因家族的成员。这种丰富的基因导致了 电压门控和配体门控的分子多样性显著 离子通道。我们正在使用一个多学科的方法来研究钠 神经中作为电信号基础的通道(NaChs) 系统。拟议的研究有两个目标：(1)继续 鉴定和鉴定新的NACH基因；(2)稍后测试 这些NACH亚型可能具有的生理作用。 我们估计老鼠(和人类一样)至少有10个nach基因。我们 已经分离并鉴定了一个全长cdna和一个 新的NaChs的部分cDNA.其中一个cdna是NACH中含量最丰富的 它在神经元和神经胶质细胞中都有表达。第二个nach是 可能只在外周神经系统表达。我们正在使用 各种分子、细胞和生物物理技术来研究 它们的分布、丰度和电生理特性 纳克斯。第二个目标围绕着一个问题，这个问题还没有 任何离子通道的答案都是：为什么会有这么多基因？一个简单的 答案是，所有子类型都有类似的通道属性，但 专门的角色。上述研究为测试提供了基础 这些NACH亚型的假设角色。将有两个函数 测试：优先针对不同的蜂窝域和 第二信使系统的差动调制。 这些研究将有助于我们对分子的理解 钠电流的组成和细胞调控。他们也会 为了解人类神经和 肌肉疾病。人类成年骨骼肌的已知突变 NACH基因会产生过度兴奋，有时还会导致一过性瘫痪。 预计其他nach基因也会发生突变，大多数 它们在神经系统中都有表达。

DESCRIPTION: Virtually all ion channels in the nervous system are members of multigene families. This abundance of genes results in a remarkable molecular diversity of both voltage-gated and ligand-gated ion channels. We are using a multidisciplinary approach to study sodium channels (NaChs) which underlie electrical signaling in the nervous system. The proposed research has two goals: (1) to continue identifying and characterizing novel NaCh genes and (2) later to test possible physiological roles subserved by these NaCh subtypes. We estimate that rats (like humans) have at least ten NaCh genes. We have isolated and are characterizing one full-length cDNA and one partial cDNA for novel NaChs. One cDNA is the most abundant NaCh in brain and is expressed in both neurons and glia. The second NaCh is probably expressed only in the peripheral nervous system. We are using a variety of molecular, cellular, and biophysical techniques to study the distribution, abundance, and electrophysiological properties of these NaChs. The second goal centers around a question which has not been answered for any ion channel: why are there so many genes? A simple answer is that all subtypes have similar channel properties but specialized roles. The above studies provide a basis for testing hypothetical roles for these NaCh subtypes. Two functions will be tested: preferential targeting to different cellular domains and differential modulation by second messenger systems. These studies will contribute to our understanding of the molecular components and cellular regulation of Na currents. They also will provide an important foundation for understanding human neural and muscular diseases. Known mutations in the human adult skeletal muscle NaCh gene produce hyperexcitability and sometimes temporary paralysis. It is expected that mutations also occur in the other NaCh genes, most of which are expressed in the nervous system.